PT  - JOURNAL ARTICLE
AU  - Singh, Anand P.
AU  - Wu, Ping
AU  - Ryabichko, Sergey
AU  - Raimundo, João
AU  - Swan, Michael
AU  - Wieschaus, Eric
AU  - Gregor, Thomas
AU  - Toettcher, Jared E.
TI  - Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation
AID  - 10.1101/2021.10.13.464280
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.13.464280
4099  - http://biorxiv.org/content/early/2021/10/14/2021.10.13.464280.short
4100  - http://biorxiv.org/content/early/2021/10/14/2021.10.13.464280.full
AB  - Developmental patterning networks are regulated by multiple inputs and feedback connections that rapidly reshape gene expression, limiting the information that can be gained solely from slow genetic perturbations. Here we show that fast optogenetic stimuli, real-time transcriptional reporters, and a simplified genetic background can be combined to reveal quantitative regulatory dynamics from a complex genetic network in vivo. We engineer light-controlled variants of the Bicoid transcription factor and study their effects on downstream gap genes in embryos. Our results recapitulate known relationships, including rapid Bicoid-dependent expression of giant and hunchback and delayed repression of Krüppel. In contrast, we find that the posterior pattern of knirps exhibits a quick but inverted response to Bicoid perturbation, suggesting a previously unreported role for Bicoid in suppressing knirps expression. Acute modulation of transcription factor concentration while simultaneously recording output gene activity represents a powerful approach for studying how gene circuit elements are coupled to cell identification and complex body pattern formation in vivo.Competing Interest StatementThe authors have declared no competing interest.